Design strategies, structure activity relationship and mechanistic insights for purines as kinase inhibitors

Sahil Sharma, Jagjeet Singh, Ritu Ojha, Harbinder Singh, Manpreet Kaur, P. M.S. Bedi, Kunal Nepali

Research output: Contribution to journalReview article

23 Citations (Scopus)

Abstract

Kinases control a diverse set of cellular processes comprising of reversible phosphorylation of proteins. Protein kinases play a pivotal role in human tumor cell proliferation, migration and survival of neoplasia. In the recent past, purine based molecules have emerged as significantly potent kinase inhibitors. In view of their promising potential for the inhibition of kinases, this review article focuses on purines which have progressed as kinase inhibitors during the last five years. A detailed account of the design strategies employed for the synthesis of purine analogs exerting inhibitory effects on diverse kinases has been presented. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the purine analogs for kinase inhibition. The interactions with the amino acid residues responsible for kinase inhibitory potential of purine based molecules have also been discussed. In this assemblage, purine based protein kinase inhibitors patented in the past have also been summarized in the tabular form. This compilation will be of great interest for the researchers working in the area of protein kinase inhibitors.

Original languageEnglish
Pages (from-to)298-346
Number of pages49
JournalEuropean Journal of Medicinal Chemistry
Volume112
DOIs
Publication statusPublished - Apr 13 2016
Externally publishedYes

Fingerprint

Purines
Structure-Activity Relationship
Phosphotransferases
Protein Kinase Inhibitors
Phosphorylation
Molecules
Cell proliferation
Protein Kinases
Cell Movement
Tumors
Neoplasms
Cell Survival
Research Personnel
Cell Proliferation
purine
Amino Acids

Keywords

  • Cancer
  • Cell lines
  • Design strategies
  • Kinases
  • Purine
  • Structure activity relationship

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Design strategies, structure activity relationship and mechanistic insights for purines as kinase inhibitors. / Sharma, Sahil; Singh, Jagjeet; Ojha, Ritu; Singh, Harbinder; Kaur, Manpreet; Bedi, P. M.S.; Nepali, Kunal.

In: European Journal of Medicinal Chemistry, Vol. 112, 13.04.2016, p. 298-346.

Research output: Contribution to journalReview article

Sharma, Sahil ; Singh, Jagjeet ; Ojha, Ritu ; Singh, Harbinder ; Kaur, Manpreet ; Bedi, P. M.S. ; Nepali, Kunal. / Design strategies, structure activity relationship and mechanistic insights for purines as kinase inhibitors. In: European Journal of Medicinal Chemistry. 2016 ; Vol. 112. pp. 298-346.
@article{41df8bf18ba048cdbe0a55eab3180d0c,
title = "Design strategies, structure activity relationship and mechanistic insights for purines as kinase inhibitors",
abstract = "Kinases control a diverse set of cellular processes comprising of reversible phosphorylation of proteins. Protein kinases play a pivotal role in human tumor cell proliferation, migration and survival of neoplasia. In the recent past, purine based molecules have emerged as significantly potent kinase inhibitors. In view of their promising potential for the inhibition of kinases, this review article focuses on purines which have progressed as kinase inhibitors during the last five years. A detailed account of the design strategies employed for the synthesis of purine analogs exerting inhibitory effects on diverse kinases has been presented. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the purine analogs for kinase inhibition. The interactions with the amino acid residues responsible for kinase inhibitory potential of purine based molecules have also been discussed. In this assemblage, purine based protein kinase inhibitors patented in the past have also been summarized in the tabular form. This compilation will be of great interest for the researchers working in the area of protein kinase inhibitors.",
keywords = "Cancer, Cell lines, Design strategies, Kinases, Purine, Structure activity relationship",
author = "Sahil Sharma and Jagjeet Singh and Ritu Ojha and Harbinder Singh and Manpreet Kaur and Bedi, {P. M.S.} and Kunal Nepali",
year = "2016",
month = "4",
day = "13",
doi = "10.1016/j.ejmech.2016.02.018",
language = "English",
volume = "112",
pages = "298--346",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",

}

TY - JOUR

T1 - Design strategies, structure activity relationship and mechanistic insights for purines as kinase inhibitors

AU - Sharma, Sahil

AU - Singh, Jagjeet

AU - Ojha, Ritu

AU - Singh, Harbinder

AU - Kaur, Manpreet

AU - Bedi, P. M.S.

AU - Nepali, Kunal

PY - 2016/4/13

Y1 - 2016/4/13

N2 - Kinases control a diverse set of cellular processes comprising of reversible phosphorylation of proteins. Protein kinases play a pivotal role in human tumor cell proliferation, migration and survival of neoplasia. In the recent past, purine based molecules have emerged as significantly potent kinase inhibitors. In view of their promising potential for the inhibition of kinases, this review article focuses on purines which have progressed as kinase inhibitors during the last five years. A detailed account of the design strategies employed for the synthesis of purine analogs exerting inhibitory effects on diverse kinases has been presented. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the purine analogs for kinase inhibition. The interactions with the amino acid residues responsible for kinase inhibitory potential of purine based molecules have also been discussed. In this assemblage, purine based protein kinase inhibitors patented in the past have also been summarized in the tabular form. This compilation will be of great interest for the researchers working in the area of protein kinase inhibitors.

AB - Kinases control a diverse set of cellular processes comprising of reversible phosphorylation of proteins. Protein kinases play a pivotal role in human tumor cell proliferation, migration and survival of neoplasia. In the recent past, purine based molecules have emerged as significantly potent kinase inhibitors. In view of their promising potential for the inhibition of kinases, this review article focuses on purines which have progressed as kinase inhibitors during the last five years. A detailed account of the design strategies employed for the synthesis of purine analogs exerting inhibitory effects on diverse kinases has been presented. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the purine analogs for kinase inhibition. The interactions with the amino acid residues responsible for kinase inhibitory potential of purine based molecules have also been discussed. In this assemblage, purine based protein kinase inhibitors patented in the past have also been summarized in the tabular form. This compilation will be of great interest for the researchers working in the area of protein kinase inhibitors.

KW - Cancer

KW - Cell lines

KW - Design strategies

KW - Kinases

KW - Purine

KW - Structure activity relationship

UR - http://www.scopus.com/inward/record.url?scp=84978793212&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978793212&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2016.02.018

DO - 10.1016/j.ejmech.2016.02.018

M3 - Review article

VL - 112

SP - 298

EP - 346

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

ER -